Transcriptional activation of c-fos protooncogene by 17beta-estradiol: mechanism of aryl hydrocarbon receptor-mediated inhibition.

17Beta-estradiol (E2) induced c-fos protooncogene mRNA levels in MCF-7 human breast cancer cells, and maximal induction was observed within 1 h after treatment. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibited the E2-induced response within 2 h. The molecular mechanism of this response was further investigated using pFC2-CAT, a construct containing a -1400 to +41 sequence from the human c-fos protooncogene linked to a bacterial chloramphenicol acetyltransferase (CAT) reporter gene. In MCF-7 cells transiently transfected with pFC2-CAT, 10 nM E2 induced an 8.5-fold increase of CAT activity, and cotreatment with 10 nM TCDD decreased this response by more than 45%. Alpha-Naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, blocked the inhibitory effects of TCDD; moreover, the inhibitory response was not observed in variant Ah-nonresponsive MCF-7 cells, suggesting that the AhR complex was required for estrogen receptor cross-talk. The E2-responsive sequence (-1220 to -1155) in the c-fos gene promoter contains two putative core pentanucleotide dioxin-responsive elements (DREs) at -1206 to -1202 and -1163 to -1159. In transient transfection assays using wild-type and core DRE mutant constructs, the downstream core DRE (at -1163 to -1159) was identified as a functional inhibitory DRE. The results of photo-induced cross-linking, gel mobility shift, and in vitro DNA footprinting assays showed that the AhR complex interacted with the core DRE that also overlapped the E2-responsive GC-rich site (-1168 to -1161), suggesting that the mechanism for AhR-mediated inhibitory effects may be due to quenching or masking at the Sp1-binding site.

[1]  S. Safe,et al.  Regulation of constitutive gene expression through interactions of Sp1 protein with the nuclear aryl hydrocarbon receptor complex. , 1999, Biochemistry.

[2]  S. Safe,et al.  Estrogen Induces Adenosine Deaminase Gene Expression in MCF-7 Human Breast Cancer Cells: Role of Estrogen Receptor-Sp1 Interactions* *This work was supported by the National Institutes of Health (Grant CA-76636), the Welch Foundation, and the Texas Agricultural Experiment Station. , 1999, Endocrinology.

[3]  S. Safe,et al.  Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. , 1998, Carcinogenesis.

[4]  S. Safe,et al.  Estrogen-induced retinoic acid receptor alpha 1 gene expression: role of estrogen receptor-Sp1 complex. , 1998, Molecular endocrinology.

[5]  R. Pollenz,et al.  Functional and physical interactions between the estrogen receptor Sp1 and nuclear aryl hydrocarbon receptor complexes. , 1998, Nucleic acids research.

[6]  B. Cochran,et al.  TFII-I Enhances Activation of the c-fosPromoter through Interactions with Upstream Elements , 1998, Molecular and Cellular Biology.

[7]  S. Safe,et al.  Estrogen-induced c-fos protooncogene expression in MCF-7 human breast cancer cells: role of estrogen receptor Sp1 complex formation. , 1998, Endocrinology.

[8]  O. Seternes,et al.  Synergistic increase in c-fos expression by simultaneous activation of the ras/raf/map kinase- and protein kinase A signaling pathways is mediated by the c-fos AP-1 and SRE sites. , 1998, Biochimica et biophysica acta.

[9]  S. Safe,et al.  Inhibition of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor growth by aryl hydrocarbon receptor agonists. , 1997, Cancer letters.

[10]  K. Rosenspire,et al.  Growth Hormone Regulates Ternary Complex Factors and Serum Response Factor Associated with the c-fos Serum Response Element* , 1997, The Journal of Biological Chemistry.

[11]  S. Safe,et al.  Functional synergy between the transcription factor Sp1 and the estrogen receptor. , 1997, Molecular endocrinology.

[12]  S. Safe,et al.  Identification of a functional imperfect estrogen-responsive element in the 5'-promoter region of the human cathepsin D gene. , 1997, Biochemistry.

[13]  S. Safe,et al.  Identification of a motif within the 5' regulatory region of pS2 which is responsible for AP-1 binding and TCDD-mediated suppression. , 1997, Biochemistry.

[14]  R. Bernards,et al.  CDK-Independent Activation of Estrogen Receptor by Cyclin D1 , 1997, Cell.

[15]  M. Kladde,et al.  Direct study of DNA‐protein interactions in repressed and active chromatin in living cells. , 1996, The EMBO journal.

[16]  L. Altucci,et al.  17 beta-Estradiol overcomes a G1 block induced by HMG-CoA reductase inhibitors and fosters cell cycle progression without inducing ERK-1 and -2 MAP kinases activation. , 1996, Oncogene.

[17]  M. Haussler,et al.  A composite element binding the vitamin D receptor, retinoid X receptor alpha, and a member of the CTF/NF-1 family of transcription factors mediates the vitamin D responsiveness of the c-fos promoter , 1996, Molecular and cellular biology.

[18]  S. Safe,et al.  Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells , 1995, Molecular and cellular biology.

[19]  G. Clark,et al.  Persistence of TCDD-induced hepatic cell proliferation and growth of enzyme altered foci after chronic exposure followed by cessation of treatment in DEN initiated female rats. , 1995, Carcinogenesis.

[20]  R. Treisman,et al.  Differential activation of c‐fos promoter elements by serum, lysophosphatidic acid, G proteins and polypeptide growth factors. , 1995, The EMBO journal.

[21]  A. Johnson,et al.  The price of repression , 1995, Cell.

[22]  P. Webb,et al.  Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens. , 1995, Molecular endocrinology.

[23]  T. Osborne,et al.  Cooperation by Sterol Regulatory Element-binding Protein and Sp1 in Sterol Regulation of Low Density Lipoprotein Receptor Gene (*) , 1995, The Journal of Biological Chemistry.

[24]  S. Safe,et al.  Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. , 1995, Pharmacology & therapeutics.

[25]  G. .. Korf,et al.  Activation of c-fos gene expression by a kinase-deficient epidermal growth factor receptor , 1994, Molecular and cellular biology.

[26]  S. Safe,et al.  Inhibition of 7,12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1994, Cancer letters.

[27]  Y. Yamasaki,et al.  Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer. , 1994, The Journal of biological chemistry.

[28]  M. Greenberg,et al.  Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB , 1994, Cell.

[29]  T. Zacharewski,et al.  Antiestrogenic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on 17 beta-estradiol-induced pS2 expression. , 1994, Cancer research.

[30]  S. Safe,et al.  Benzo[a]pyrene-resistant MCF-7 human breast cancer cells. A unique aryl hydrocarbon-nonresponsive clone. , 1994, The Journal of biological chemistry.

[31]  G. Segre,et al.  Parathyroid hormone induces sequential c-fos expression in bone cells in vivo: in situ localization of its receptor and c-fos messenger ribonucleic acids. , 1994, Endocrinology.

[32]  M. Green,et al.  HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. , 1993, Science.

[33]  D. Meyer,et al.  The serum response element can mediate induction of c-fos by growth hormone. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Bennett,et al.  Correlation of in vitro and in vivo growth suppression of MCF-7 human breast cancer by 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1993, Cancer Research.

[35]  S. Safe,et al.  Mechanism of action of α-naphthoflavone as an Ah receptor antagonist in MCF-7 human breast cancer cells , 1993 .

[36]  F. Bresciani,et al.  Estrogen regulation of proto-oncogenes coding for nuclear proteins. , 1993, Critical reviews in oncogenesis.

[37]  H. Rochefort,et al.  Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  W. Kruijer,et al.  Oestrogen directly stimulates growth factor signal transduction pathways in human breast cancer cells , 1991, The Journal of Steroid Biochemistry and Molecular Biology.

[39]  R. St-Arnaud,et al.  Differential stimulation of fos and jun family members by calcitriol in osteoblastic cells. , 1991, Molecular endocrinology.

[40]  E. Milgrom,et al.  Characterization of the hormone responsive element involved in the regulation of the progesterone receptor gene. , 1991, The EMBO journal.

[41]  P. Chambon,et al.  Activation of the ovalbumin gene by the estrogen receptor involves the Fos-Jun complex , 1990, Cell.

[42]  B. van der Burg,et al.  Stimulation of TPA-responsive element activity by a cooperative action of insulin and estrogen in human breast cancer cells. , 1990, Molecular endocrinology.

[43]  A. Weisz,et al.  Identification of an estrogen response element upstream of the human c-fos gene that binds the estrogen receptor and the AP-1 transcription factor. , 1990, Nucleic acids research.

[44]  M E Greenberg,et al.  Growth factor-induced gene expression: the ups and downs of c-fos regulation. , 1990, The New biologist.

[45]  L. Matrisian,et al.  Epidermal growth factor stimulation of stromelysin mRNA in rat fibroblasts requires induction of proto-oncogenes c-fos and c-jun and activation of protein kinase C , 1990, Molecular and cellular biology.

[46]  M. Sheng,et al.  The inner core of the serum response element mediates both the rapid induction and subsequent repression of c-fos transcription following serum stimulation. , 1990, Genes & development.

[47]  B. Burg,et al.  Direct effects of estrogen on c-fos and c-myc protooncogene expression and cellular proliferation in human breast cancer cells , 1989, Molecular and Cellular Endocrinology.

[48]  H. Rochefort,et al.  Regulation of cathepsin-D and pS2 gene expression by growth factors in MCF7 human breast cancer cells. , 1989, Molecular endocrinology.

[49]  A. Nordheim,et al.  The ability of a ternary complex to form over the serum response element correlates with serum inducibility of the human c-fos promoter , 1989, Cell.

[50]  T. Curran,et al.  The structure and function of the fos proto-oncogene. , 1989, Critical reviews in oncogenesis.

[51]  B. Franza,et al.  Fos and jun: The AP-1 connection , 1988, Cell.

[52]  T. Hunter,et al.  The c-fos protein interacts with c-Jun AP-1 to stimulate transcription of AP-1 responsive genes , 1988, Cell.

[53]  E. Gelmann,et al.  Effects of steroid hormones and peptide growth factors on protooncogene c-fos expression in human breast cancer cells. , 1988, Cancer research.

[54]  B. Spiegelman,et al.  Common DNA binding site for Fos protein complexesand transcription factor AP-1 , 1988, Cell.

[55]  R. Roeder,et al.  c-fos sequence necessary for basal expression and induction by epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate and the calcium ionophore , 1987, Molecular and cellular biology.

[56]  I. Verma,et al.  The fos oncogene. , 1987, Advances in cancer research.

[57]  R. Müller.  Cellular and viral fos genes: structure, regulation of expression and biological properties of their encoded products. , 1986, Biochimica et biophysica acta.

[58]  C. Wade,et al.  Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. , 1978, Toxicology and applied pharmacology.